Teeth are one of the tissues in the body that undergo biomineralization, the process by which living organisms secrete inorganic minerals in the form of biominerals within body tissue and/or structures. Teeth have four major components: enamel, dentin (or dentine), cementum and pulp. The enamel of a tooth is the intensely hard calcareous (i.e., calcium based) substance that forms a thin layer which caps or partly covers the teeth of most mammals, including humans and other vertebrates. Dentin also comprises calcareous material. It is usually covered by enamel on the crown and cementum on the root and surrounds the entire pulp (i.e., the living tissue of the tooth). Dentin is a living tissue comprised of a mineralized matrix p minute tubules which enter into the inner cavity of the tooth where the pulp is housed. The major organic component of dentin is type I collagen. Type I collagen forms a three-dimensional network within which deposition of noncollagenous proteins and the nucleation of hydroxyapatite crystals occur. The cementum is a thin, fairly hard bone tissue covering the root of the tooth.
Dental caries, also known as tooth decay or cavity, is one of the most ubiquitous bacterial infections in world. Dental caries is a disease wherein bacterial processes damage hard tooth structure (enamel, dentin and cementum). Remineralization of structurally intact dentin matrix previously demineralized by dental caries and the treatment of dental caries by the creation of dental fillings is of imminent concern from public health and research perspectives. Similar to bone, the apatite phase in mineralized dentin is classified as either intrafibrillar, referring to the hole zones and pore spaces within the collagen fibrils, and interfibrillar, referring to the interstitial spaces separating the individual collagen fibrils. (US 2006-0204581; Traub, W. et al., Matrix, 1992, 12:251-255; Landis, W. J. et al., Microsc. Res. Tech., 1996, 33:192-202).
To date, the treatment of dental caries is focused mainly on a surgical model of removing the carious tooth structure followed by replacement with an inert restorative material. Once dental caries is found in a tooth, the typical therapy is to remove the caries. Therapy for cavities formed by decay is typically referred to as a “filling” or resin bonding. Dentin bonding is a unique form of tissue engineering in which a demineralized collagen matrix continuous with the underlying mineralized dentin is created via acid-etching or acidic self-etching adhesives and used as the scaffold for resin infiltration. In accordance with this procedure, a dentist or other authorized practitioner may use a drill or a laser to remove the carious dental tissue and may also form undercuts in order to secure the filling material. The cut surface of the tooth is acid etched and the dentist then fills the cavity with a restorative material to replace the portion of the tooth lost to decay, the restorative material becoming bonded to the tooth tissue. This filling material is placed downward into the tooth from the upper or crown regions of the tooth. Alternatively, the carious dental tissue itself may be acid etched without invasive removal of carious dental tissue prior to application of the restorative material. Restorative material may be adhered to teeth using dental adhesives, which rely on micromechanical entanglement of resin polymers within partially or completely demineralized collagen matrices for retention of the resin composite fillings. (Vaidyanathan and Vaidyanathan, J. Biomed. Mater. Res. B Appl. Biomater. 2009, 82:558-578) Infiltration of resins into the demineralized dentin creates a so-called interdiffusion zone or hybrid layer.
Despite significant improvements in contemporary resin composites and their bonding to tooth structures via the use of dentin adhesives, it is estimated that half of all resin composite restorations fail within 10 years. Replacement of failed composite restorations accounts for 50-70% of all restorations and replacing them consumes 60% of the dentist's practice time. Secondary caries at the tooth-restoration margins is a major reason for the replacement of existing restorations. Composite-dentin bonds are continuously challenged by the harsh mechanical and chemical environment of the oral cavity, with the risk of secondary caries being 3.5 times higher in resin composite than in amalgam restorations (Bernardo et al., J. Am. Dent. Assoc., 2007, 138:775-783). As replacement dentistry costs about 5 billion dollars annually in the United States alone, there is a compelling need to pursue alternative methods to preserve resin-dentin bond integrity and extend the longevity of resin-based restorations.
Unstable bonding of resin-based fillings to teeth is partly due to the proteinaceous nature of dentin, which can result in incomplete infiltration of the resin into the tooth structure. The most compelling problem associated with resin-dentin bonds is limited durability (De Munck, J. et al., J. Dent. Res., 2005, 84:118-132), which can be caused partially by water sorption-induced hydrolysis of the hydrophilic resin components present in these adhesives (Ito, S. et al., Biomaterials, 2005, 26:6449-6459), and partially by degeneration of collagen fibrils via endogenous matrix metalloproteinases (MMPs) derived from the demineralized dentin (Pashley, D. H. et al., J. Dent. Res., 2004, 83:216-221). While hydrophilic resin monomers are conventionally thought to be important for bonding of resins to dentin, their inclusion in restorative materials may cause the resulting resin-dentin bonds to be susceptible to degradation via water sorption, hydrolysis of resin ester linkages and activation of endogenous collagen degrading enzymes (Breschi et al. Dent. Mater., 2008, 24:90-101).
When tooth dentin becomes demineralized, especially from the caries process, the dentin loses its mechanical properties and becomes softer, weaker and less stiff. Such dentin often loses half its mineral phase that is replaced by water. This weakened dentin provides a poor foundation for crowns, bridges and restorative materials. Thus, mineralization of dental tissue weakened by dental caries and/or acid-etching-demineralization is desirable to strengthen tooth structure. Heterogeneous deposition of calcium phosphate minerals in interfibrillar collagen spaces alone does not result in a highly mineralized collagen matrix and, in the absence of intrafibrillar dentin mineralization, the hardness and modulus of elasticity in carious dentin is inferior to those of sound dentin (Kinney, J. H., et al., J. Dent. Res., 2003, 82:957-961); Jäger, I. et al., Biophy. J., 2000, 79:1737-1746. Therefore, in order to produce remineralized dentin comparable to that of sound dentin, both interfibrillar and intrafibrillar remineralization may be required.
Thus, development of remineralization approaches for dental caries, as well as improvement of resin-dentin bonding (i.e., for fillings) is highly desirable. In the case of caries, apatite crystals that are present within and surrounding the enamel, dentin and cementum tissues can serve as the nuclei for apatite crystal deposition. However, in the case of resin-dentin bonds, there are zones of completely demineralized dentin adjacent to the resin surface within which apatite crystal deposition must be initiated de novo.